Possible contribution of CD44 variant 6 and nuclear beta-catenin expression to the formation of budding tumor cells in patients with T1 colorectal carcinoma

Cancer. 2001 Nov 15;92(10):2539-46. doi: 10.1002/1097-0142(20011115)92:10<2539::aid-cncr1605>3.0.co;2-i.


Background: In an earlier study, the authors demonstrated that tumor budding was useful for predicting lymph node metastasis in patients with early invasive (T1) colorectal carcinoma. This study was undertaken to clarify the associations between tumor budding, E-cadherin-catenin complex, and CD44 variant 6 abnormalities.

Methods: In 51 T1 colorectal carcinomas, tumor budding (the number of dedifferentiation units at the invasive margin) on hematoxylin and eosin-stained slides was counted under light microscopy. Immunostaining for E-cadherin, alpha-catenin, beta-catenin, and CD44 variant 6 was performed on formalin fixed, paraffin embedded sections. The associations between locoregional failure (lymph node metastasis or local recurrence) and tumor budding and clinicopathologic parameters and immunoreactivity were examined statistically.

Results: In univariate analysis, tumor budding and nuclear beta-catenin expression were associated significantly with locoregional failure (P = 0.004, 0.01). Multivariate analysis showed that tumor budding alone was associated significantly with locoregional failure (P = 0.02), and the association between nuclear beta-catenin expression and locoregional failure was marginally significant (P = 0.07). Analysis of variance showed that lymphatic invasion alone was associated significantly with tumor budding (P = 0.02), and there was a significant interaction effect for tumor budding between CD44 variant 6 expression and nuclear beta-catenin expression (P = 0.01). There was a significant correlation between expression patterns of these two molecules and locoregional failure (P = 0.01).

Conclusions: The current results suggest that the up-regulation of CD44 variant 6 through nuclear beta-catenin activation may contribute to the formation of tumor budding, and immunostaining of these two adhesion molecules may be useful in identifying those at high-risk for locoregional failure among patients with T1 colorectal carcinoma.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma / genetics
  • Carcinoma / pathology*
  • Cell Differentiation*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / pathology*
  • Cytoskeletal Proteins / analysis
  • Cytoskeletal Proteins / biosynthesis*
  • Cytoskeletal Proteins / pharmacology
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic
  • Glycoproteins / analysis
  • Glycoproteins / biosynthesis*
  • Glycoproteins / pharmacology
  • Humans
  • Hyaluronan Receptors / analysis
  • Hyaluronan Receptors / biosynthesis*
  • Hyaluronan Receptors / pharmacology
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Neoplasm Invasiveness / physiopathology*
  • Neoplasm Recurrence, Local
  • Risk Factors
  • Trans-Activators*
  • Up-Regulation
  • beta Catenin


  • CD44v6 antigen
  • CTNNB1 protein, human
  • Cytoskeletal Proteins
  • Glycoproteins
  • Hyaluronan Receptors
  • Trans-Activators
  • beta Catenin